Cytolysin-mediated translocation (CMT): A functional equivalent of type III secretion in Gram-positive bacteria

Type III secretion for injection of effector proteins into host cells has n ot been described for Gram-positive bacteria despite their importance in di sease. Here, we describe an injection pathway for the Gram-positive pathoge n Streptococcus pyogenes that utilizes streptolysin O (SLO), a cholesterol- dependent cytolysin. The data support a model in which an effector is trans located through the SLO pore by a polarized process. The effector, SPN (S. pyogenes NAD-glycohydrolase), is capable of producing the potent second mes senger cyclic ADP-ribose, and SLO and SPN act synergistically to trigger cy totoxicity. These data provide a novel paradigm for the function of the cho lesterol-dependent cytolysin family and its wide distribution suggests that cytolysin-mediated translocation (CMT) may be the equivalent of type III s ecretion for Gram-positive pathogens.